# Esclerose lateral amiotrófica

> Página oficial: https://raras.org/doenca/esclerose-lateral-amiotrofica
> Fonte: Raras.org — Banco de Dados de Doenças Raras em Português (CC BY-NC-SA 4.0)
> Última atualização: 2026-05-07

## Identificadores

- **ORPHA**: 803 — https://www.orpha.net/en/disease/detail/803
- **CID-10**: G12.2
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

A esclerose lateral amiotrófica (ELA) é uma doença neurodegenerativa caracterizada por paralisia muscular progressiva reflectindo degenerescência dos neurónios motores no córtex motor primário, vias corticoespinhais, tronco cerebral e medula espinhal.

## Epidemiologia e herança

- **Prevalência**: 1-9 / 100 000
- **Padrão de herança**: Autosomal dominant, Autosomal recessive, Not applicable

## Sinais e sintomas (245 fenótipos HPO)

- **Fraqueza fatigável dos músculos bulbares** — HPO: HP:0030192 (Frequente (79-30%))
- **Distonia axial** — HPO: HP:0002530
- **Morfologia anormal do cerebelo** — HPO: HP:0001317
- **Atrofia da fibra muscular** — HPO: HP:0100295
- **Contratura das articulações dos membros superiores** — HPO: HP:0100360
- **Habilidade atrasada de andar** — HPO: HP:0031936
- **Distonia oromandibular** — HPO: HP:0012048
- **Alimentação por gastrostomia na infância** — HPO: HP:0011471
- **Fraqueza dos flexores do pescoço** — HPO: HP:0003722
- **Contratura das articulações dos membros inferiores** — HPO: HP:0005750
- **Hipomielinização do SNC** — HPO: HP:0003429
- **Incapacidade de andar** — HPO: HP:0002540
- **Giração cortical anormal** — HPO: HP:0002536
- **Atrofia da camada de Purkinje cerebelar** — HPO: HP:0012082
- **Perda de mielina nas colunas posteriores da medula espinhal** — HPO: HP:0008311
- **Hipoplasia olivopontocerebelar** — HPO: HP:0006955
- **Anormalidade da substância negra** — HPO: HP:0045007
- **Anormalidade dos tratos espinocerebelares** — HPO: HP:0003133
- **Reflexos tendinosos profundos hiperativos** — HPO: HP:0006801
- **Morfologia celular anormal** — HPO: HP:0025461
- **Coreia** — HPO: HP:0002072
- **Atrofia da substância branca cerebral** — HPO: HP:0012762
- **Oftalmoparesia** — HPO: HP:0000597
- **Tremor cinético** — HPO: HP:0030186
- **Oftalmoplegia supranuclear** — HPO: HP:0000623
- **Ataxia da marcha** — HPO: HP:0002066
- **Amplitude diminuída do potencial de ação muscular composto** — HPO: HP:0033383
- **Atrofia da medula espinhal** — HPO: HP:0006827
- **Reflexo de Chaddock** — HPO: HP:0010875
- **Dificuldade para ficar em pé** — HPO: HP:0003698
- **Edema axonal difuso** — HPO: HP:0003405
- **Palidez das colunas dorsais da medula espinhal** — HPO: HP:0006825
- **Degeneração axonal** — HPO: HP:0040078
- **Degeneração axonal periférica** — HPO: HP:0000764
- **Dificuldade para subir escadas** — HPO: HP:0003551
- **Mialgia** — HPO: HP:0003326
- **Reflexos tendíneos reduzidos** — HPO: HP:0001315
- **Perda da fala** — HPO: HP:0002371
- **Discinesia orofacial** — HPO: HP:0002310
- **Hiperoralidade** — HPO: HP:0000710
- _...e mais 205 sintomas. Ver https://raras.org/doenca/esclerose-lateral-amiotrofica._

## Genes associados (46)

- **TREM2** — Triggering receptor expressed on myeloid cells 2 [Major susceptibility factor in]
  - Função: Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ
- **LRP12** — Low-density lipoprotein receptor-related protein 12 [Disease-causing germline mutation(s) in]
  - Função: Probable receptor, which may be involved in the internalization of lipophilic molecules and/or signal transduction. May act as a tumor suppressor
- **ALS2** — Alsin [Disease-causing germline mutation(s) in]
  - Função: May act as a GTPase regulator. Controls survival and growth of spinal motoneurons (By similarity)
- **TIA1** — Cytotoxic granule associated RNA binding protein TIA1 [Disease-causing germline mutation(s) in]
  - Função: RNA-binding protein involved in the regulation of alternative pre-RNA splicing and mRNA translation by binding to uridine-rich (U-rich) RNA sequences (PubMed:11106748, PubMed:12486009, PubMed:17488725
- **SPG11** — Spatacsin [Disease-causing germline mutation(s) in]
  - Função: May play a role in neurite plasticity by maintaining cytoskeleton stability and regulating synaptic vesicle transport
- **SPTLC1** — Serine palmitoyltransferase 1 [Disease-causing germline mutation(s) in]
  - Função: Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (mos
- **TUBA4A** — Tubulin alpha-4A chain [Disease-causing germline mutation(s) in]
  - Função: Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the additio
- **SETX** — Helicase senataxin [Disease-causing germline mutation(s) in]
  - Função: ATP-dependent 5'->3' DNA/RNA helicase that preferentially unwinds RNA substrates over DNA, playing a crucial role in resolving R-loops and promoting transcription termination (PubMed:36864660). Plays
- **CYLD** — Ubiquitin carboxyl-terminal hydrolase CYLD [Disease-causing germline mutation(s) in]
  - Função: Deubiquitinase that specifically cleaves 'Lys-63'- and linear 'Met-1'-linked polyubiquitin chains and is involved in NF-kappa-B activation and TNF-induced necroptosis (PubMed:18313383, PubMed:18636086
- **SIGMAR1** — Sigma non-opioid intracellular receptor 1 [Disease-causing germline mutation(s) in]
  - Função: Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma memb
- **C9orf72** — Guanine nucleotide exchange factor C9orf72 [Disease-causing germline mutation(s) in]
  - Função: Acts as a guanine-nucleotide releasing factor (GEF) for Rab GTPases by promoting the conversion of inactive RAB-GDP to the active form RAB-GTP (PubMed:27103069, PubMed:27193190, PubMed:27617292, PubMe
- **GLE1** — mRNA export factor GLE1 [Disease-causing germline mutation(s) in]
  - Função: Required for the export of mRNAs containing poly(A) tails from the nucleus into the cytoplasm. May be involved in the terminal step of the mRNA transport through the nuclear pore complex (NPC)
- **ERBB4** — Receptor tyrosine-protein kinase erbB-4 [Disease-causing germline mutation(s) in]
  - Função: Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary
- **FIG4** — Polyphosphoinositide phosphatase [Disease-causing germline mutation(s) in]
  - Função: Dual specificity phosphatase component of the PI(3,5)P2 regulatory complex which regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) (PubMed:17556371, Pu
- **PRPH** — Peripherin-2 [Major susceptibility factor in]
  - Função: Essential for retina photoreceptor outer segment disk morphogenesis, may also play a role with ROM1 in the maintenance of outer segment disk structure (By similarity). Required for the maintenance of

## Medicamentos em desenvolvimento (4)

- TOFERSEN — Fase Phase 4 (SOD1 mRNA antisense inhibitor)
- RILUZOLE — Fase Phase 4 (Sodium channel alpha subunit blocker)
- MECASERMIN — Fase Phase 3 (Insulin-like growth factor I receptor agonist)
- QUINIDINE — Fase Phase 3 (Sodium channel alpha subunit blocker)
- Fonte: https://platform.opentargets.org/disease/MONDO_0004976

## Ensaios clínicos ativos (38)

- **NCT07467187** [RECRUITING]: Invasive Home Ventilation in Denmark — https://clinicaltrials.gov/study/NCT07467187
- **NCT03225144** [RECRUITING]: Investigating Complex Neurodegenerative Disorders Related to Amyotrophic Lateral Sclerosis and Frontotemporal Dementia — https://clinicaltrials.gov/study/NCT03225144
- **NCT07161999** [RECRUITING]: Study of COYA 302 for the Treatment of ALS — https://clinicaltrials.gov/study/NCT07161999
- **NCT05747937** [RECRUITING]: Longitudinal Assessment of Autonomic and Sensory Nervous System in ALS — https://clinicaltrials.gov/study/NCT05747937
- **NCT04297683** [RECRUITING]: HEALEY ALS Platform Trial - Master Protocol — https://clinicaltrials.gov/study/NCT04297683
- **NCT07357428** [RECRUITING]: Connect-One: Early Feasibility Study of Connexus® Brain-Computer Interface (BCI) — https://clinicaltrials.gov/study/NCT07357428
- **NCT07017946** [RECRUITING]: Intestinal Microbiome Transplant in ALS — https://clinicaltrials.gov/study/NCT07017946
- **NCT05204017** [RECRUITING]: Comprehensive Analysis Platform To Understand, Remedy and Eliminate ALS — https://clinicaltrials.gov/study/NCT05204017
- **NCT06450691** [RECRUITING]: Modeling Amyotrophic Lateral Sclerosis With Fibroblasts — https://clinicaltrials.gov/study/NCT06450691
- **NCT07287397** [RECRUITING]: Study is to Assess the Safety and Tolerability of VTx-002 in Participants With ALS — https://clinicaltrials.gov/study/NCT07287397

## Doenças relacionadas (por similaridade fenotípica)

- [Demência fronto-temporal](https://raras.org/doenca/demencia-fronto-temporal) — ORPHA:282 — 84 sintomas em comum
- [Esclerose lateral amiotrófica juvenil](https://raras.org/doenca/esclerose-lateral-amiotrofica-juvenil) — ORPHA:300605 — 77 sintomas em comum
- [Ataxia espástica](https://raras.org/doenca/ataxia-espastica) — ORPHA:316226 — 72 sintomas em comum
- [Demência frontotemporal com doença do neurônio motor](https://raras.org/doenca/demencia-frontotemporal-com-doenca-do-neuronio-motor) — ORPHA:275872 — 66 sintomas em comum
- [Miopatia distal autossômica dominante](https://raras.org/doenca/miopatia-distal-autossomica-dominante) — ORPHA:206650 — 62 sintomas em comum
- [NÃO RARA NA EUROPA: Doença de Parkinson](https://raras.org/doenca/nao-rara-na-europa-doenca-de-parkinson) — ORPHA:319705 — 62 sintomas em comum
- [Miopatia de inclusão](https://raras.org/doenca/miopatia-de-inclusao) — ORPHA:206662 — 61 sintomas em comum
- [Ataxia cerebelosa ligada ao X](https://raras.org/doenca/ataxia-cerebelosa-ligada-ao-x) — ORPHA:247765 — 60 sintomas em comum
- [Gangliosidose GM2](https://raras.org/doenca/gangliosidose-gm2) — ORPHA:309152 — 60 sintomas em comum
- [Atrofia muscular espinhal proximal](https://raras.org/doenca/atrofia-muscular-espinhal-proximal) — ORPHA:70 — 59 sintomas em comum

## Importante

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Pacientes devem consultar profissionais de saúde qualificados para decisões clínicas.

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